FDG PET/CT and Endoscopic Ultrasound for Preoperative T-Staging of Esophageal Squamous Cell Carcinoma.

This study aimed to compare the diagnostic performances of endoscopic ultrasound (EUS) and FDG PET/CT in the preoperative T-staging of esophageal squamous cell carcinoma (ESCC) and determine whether their innovative coordination achieves better prediction. In total, 100 patients diagnosed with ESCC, 57 without (CRT[-]sub) and 43 with (CRT[+]sub) neoadjuvant chemoradiotherapy, undergoing EUS and FDG PET/CT, followed by surgical resection of the tumor, were included in this analysis. EUS classified T-stages based on the depth of primary tumor invasion, and FDG PET/CT used thresholded maximal standardized uptake value (SUVmax) classifications. By employing pathology results as the reference standard, we assessed the accuracy of EUS and FDG PET/CT, evaluated their concordance using the κ statistic, and conducted a comparative analysis between the two modalities through McNemar's chi-square test. FDG PET/CT had higher overall accuracy than EUS (for CRT[-]sub: 71.9%, κ = 0.56 vs. 56.1%, κ = 0.31, p = 0.06; for CRT[+]sub: 65.1%, κ = 0.50 vs. 18.6%, κ = 0.05, p < 0.01) in predicting pT- and ypT-stage. Our proposed method of incorporating both FDG PET/CT and EUS information could achieve higher accuracies in differentiating between early and locally advanced disease in the CRT[-]sub group (82.5%) and determining residual viable tumor in the CRT[+]sub group (83.7%) than FDG PET/CT or EUS alone. FDG PET/CT had a better diagnostic ability than EUS to predict the (y)pT-stage of ESCC. Our complementary method, which combines the advantages of both imaging modalities, can deliver higher accuracy for clinical applications of ESCC.

Reduced mitochondria membrane potential and lysosomal acidification are associated with decreased oligomeric Aß degradation induced by hyperglycemia: A study of mixed glia cultures.

Diabetes is a risk factor for Alzheimer's disease (AD), a chronic neurodegenerative disease. We and others have shown prediabetes, including hyperglycemia and obesity induced by high fat and high sucrose diets, is associated with exacerbated amyloid beta (Aß) accumulation and cognitive impairment in AD transgenic mice. However, whether hyperglycemia reduce glial clearance of oligomeric amyloid-ß (oAß), the most neurotoxic Aß aggregate, remains unclear. Mixed glial cultures simulating the coexistence of astrocytes and microglia in the neural microenvironment were established to investigate glial clearance of oAß under normoglycemia and chronic hyperglycemia. Ramified microglia and low IL-1ß release were observed in mixed glia cultures. In contrast, amoeboid-like microglia and higher IL-1ß release were observed in primary microglia cultures. APPswe/PS1dE9 transgenic mice are a commonly used AD mouse model. Microglia close to senile plaques in APPswe/PS1dE9 transgenic mice exposed to normoglycemia or chronic hyperglycemia exhibited an amoeboid-like morphology; other microglia were ramified. Therefore, mixed glia cultures reproduce the in vivo ramified microglial morphology. To investigate the impact of sustained high-glucose conditions on glial oAß clearance, mixed glia were cultured in media containing 5.5 mM glucose (normal glucose, NG) or 25 mM glucose (high glucose, HG) for 16 days. Compared to NG, HG reduced the steady-state level of oAß puncta internalized by microglia and astrocytes and decreased oAß degradation kinetics. Furthermore, the lysosomal acidification and lysosomal hydrolysis activity of microglia and astrocytes were lower in HG with and without oAß treatment than NG. Moreover, HG reduced mitochondrial membrane potential and ATP levels in mixed glia, which can lead to reduced lysosomal function. Overall, continuous high glucose reduces microglial and astrocytic ATP production and lysosome activity which may lead to decreased glial oAß degradation. Our study reveals diabetes-induced hyperglycemia hinders glial oAß clearance and contributes to oAß accumulation in AD pathogenesis.

Case report: Durable response after pembrolizumab in combination with radiation - induced abscopal effect in platinum - refractory metastatic endometrial clear cell carcinoma.

Advanced endometrial clear cell carcinoma (CCC) tends to have poor prognosis owing to aggressive clinical behavior and poor response to conventional chemotherapy. Herein, we report a case of platinum-refractory recurrent ECCC successfully treated with the combination of pembrolizumab, localized radiotherapy and a few cycles of chemotherapy with an extremely durable response even after cessation of immunotherapy for 3 years at the time of publication.

A proactive remote pharmaceutical care for rural elderly population: The Houston-Apollo polypharmacy project.

AIMS: To evaluate polypharmacy-related problems in the elderly people who live in rural through a proactive pharmaceutical care project under a novel remote medical service infrastructure (the Houston-Apollo polypharmacy project). METHODS: It is a prospectively cross-sectional study. The elderly aged 65 years old lived in communities executed the congregate meal service and joined the Houston-Apollo project were included. During March and July on 2020, the pharmaceutical care team of Houston-Apollo polypharmacy project interviewed old people and collected their medications by remote video. Polypharmacy situation and drug-related problems, including potentially inappropriate medications (PIMs), anticholinergic burden (ACB) and risk of sarcopaenia, were evaluated by clinical pharmacists. In addition, we analysed the categories of the prescription types between polypharmacy and non-polypharmacy users, polypharmacy users with and without PIMs or ACB. A patient-specific integrated pharmacist's note for medication education and a dear doctor letter (as needed) were generated and delivered within 2-weeks postinterviewed. Age- and sex-adjusted logistic regression model was used to evaluate the association between polypharmacy and these potential medication problems. RESULTS: There were 87 older people (mean age = 75.9) and 536 long-term medications were collected. Among them, 52% were defined as polypharmacy users. Polypharmacy was significantly associated with higher risk of PIMs and ACB. The adjusted odd ratio was 5.31 (95% CI: 2.02-13.9) and 10.1 (95% CI: 3.4-29.7), respectively. Among polypharmacy users, there were nearly double the prescriptions for the nervous system and musculoskeletal system among patients with PIMs compared with those without PIMs. Besides, polypharmacy users with ACB showed higher rate of prescriptions for the nervous system and the alimentary tract and metabolism system compared with those without ACB. CONCLUSION: Polypharmacy was significantly associated with negative impact of medication safety among the elderly people in rural area. A persistent remote pharmaceutical care intervention was crucial for improving this problem.

The feasibility of anterior 180° 99m Tc-sestamibi parathyroid SPECT/CT.

OBJECTIVE: For 99mTc-sestamibi parathyroid single photon emission computed tomography/computed tomography (SPECT/CT), the traditional full-arc 360° acquisition technique has been suggested but not the theoretically low tissue-attenuated anterior 180° method. We aimed to compare the diagnostic performances and target-to-background ratios of anterior 180° and 360° SPECT/CT imaging. METHODS: Ninety-nine patients who underwent 99mTc-sestamibi scintigraphy and received a surgical-pathological diagnosis of parathyroid adenoma or hyperplasia were enrolled. The SPECT/CT reconstructed images with anterior 180° and full-arc 360° data were interpreted by two physicians using a scoring scale, and the lesions were semi-quantified using target-to-background ratios for both image sets. RESULTS: In total, 113 abnormal parathyroid lesions were identified on the SPECT/CT images. The agreements of interpretation between the two image sets and readers were very good (κ value: 0.83-1.00). The accuracies of summative interpretation for the anterior 180° and full-arc 360° SPECT/CT were 83.04% and 82.46%, respectively. The target-to-background ratios were significantly higher for the anterior 180° than the full-arc 360° images (P < 0.01). CONCLUSIONS: The anterior 180° SPECT/CT technique, a time-saving method, can provide satisfactory diagnostic performance and superior lesion contrast compared with the full-arc 360° SPECT/CT technique in 99mTc-sestamibi parathyroid imaging.

Effect of fasting duration on myocardial fluorodeoxyglucose uptake in diabetic and nondiabetic patients.

OBJECTIVE: To detect cardiac hypermetabolic lesions using fluorodeoxyglucose (FDG) with PET/computed tomography (PET/CT), the efficiency of long fasting and temperature condition for lowering physiological myocardial FDG uptake is controversial and may be confounded by other factors. We thus aimed to investigate the impact of fasting duration and ambient temperature on myocardial uptake in diabetic and nondiabetic patients. METHODS: FDG PET/CT scans (n = 666) were reviewed and the myocardial uptake was visually graded on a four-point scale and quantified using standardized uptake value (SUV). The associations between myocardial uptake and fasting duration, diabetes status, ambient temperature parameters, age, gender, and BMI were evaluated. RESULTS: Intraobserver [κ = 0.94; intraclass correlation coefficient (ICC) = 0.99] and interobserver (κ = 0.91; ICC = 0.99) reliabilities of both visual and SUV measurements were all excellent. Fasting duration and diabetes status were found to be significantly associated with myocardial FDG uptake, but the ambient temperature parameters and other factor were not. Patients with intense (Grade 4) myocardial uptake had a shorter fasting duration (P = 0.011). The SUVmax of myocardium was significantly higher in nondiabetic than diabetic patients (P < 0.001). Fasting duration ≥ 12 h in diabetic and ≥16 h in nondiabetic patients was associated with low prevalence of Grade 4 uptake (4.2%, P = 0.016; 2.3%, P = 0.028). CONCLUSION: Fasting for long enough durations but not ambient temperature was associated with decreased physiological myocardial FDG uptake. A fasting duration of more than 12 h for diabetic, 16 h for nondiabetic patients is a simple and valuable recommendation.

Combining fluorine-18 fluorodeoxyglucose positron emission tomography and pathological risk factors to predict postoperative recurrence in stage I lung adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the predictive value of qualitative assessment of tumor fluorine-18 fluorodeoxyglucose (F-FDG) uptake on PET and pathological risk factors for postoperative tumor recurrence in patients with stage I lung adenocarcinoma. PATIENTS AND METHODS: Eighty-seven patients with stage I lung adenocarcinoma who had undergone F-FDG-PET and sequential surgical treatment without adjuvant chemotherapy were enrolled into this retrospective study. Qualitative assessment visually compared tumor F-FDG uptake with liver uptake. Tumors with one or more risk factors of tumor size of at least 4 cm, poorly differentiated, visceral pleural invasion, and lymphovascular invasion were defined as pathological high-risk tumors. RESULTS: Patients with pathological high-risk tumors had a significantly (P=0.015) higher standardized uptake value. A multivariable Cox's proportional hazard analysis showed that tumor F-FDG uptake>liver uptake (adjusted hazard ratio: 3.54; 95% confidence interval: 1.36-9.21, P=0.010) and pathological high-risk tumors (adjusted hazard ratio: 2.34; 95% confidence interval: 1.13-4.87, P=0.023) were significant independent predictors of postoperative tumor recurrence. Patients with tumor F-FDG uptake>liver uptake and pathological high-risk tumors had significantly (P=0.001) worse 5-year disease-free survival (38.8%) and significantly (P=0.011) worse overall survival (68.5%). CONCLUSION: Tumor F-FDG uptake>liver uptake and pathological high-risk tumors were significant independent predictors of postoperative tumor recurrence in stage I lung adenocarcinoma. Combining the two factors improves the prediction of disease-free and overall survivals, which could offer a feasible prediction model for clinically recommending adjuvant chemotherapy.

Post-chemoradiotherapy FDG PET with qualitative interpretation criteria for outcome stratification in esophageal squamous cell carcinoma.

OBJECTIVES: Post-chemoradiotherapy (CRT) FDG PET is a useful prognosticator of esophageal cancer. However, debate on the diverse criteria of previous publications preclude worldwide multicenter comparisons, and even a universal practice guide. We aimed to validate a simple qualitative interpretation criterion of post-CRT FDG PET for outcome stratification and compare it with other criteria. METHODS: The post-CRT FDG PET of 114 patients with esophageal squamous cell carcinoma (ESCC) were independently interpreted using a qualitative 4-point scale (Qual4PS) that identified focal esophageal FDG uptake greater than liver uptake as residual tumor. Cohen's κ coefficient (κ) was used to measure interobserver agreement of Qual4PS. The Kaplan-Meier method and Cox proportional hazards regression analyses were used for survival analysis. Other criteria included a different qualitative approach (QualBK), maximal standardized uptake values (SUVmax3.4, SUVmax2.5), relative change of SUVmax between pre- and post-CRT FDG PET (ΔSUVmax), mean standardized uptake values (SUVmean), metabolic volume (MV) and total lesion glycolysis (TLG). RESULTS: Overall interobserver agreement on the Qual4PS criterion was excellent (κ: 0.95). Except the QualBK, SUVmax2.5, and TLG, all the other criteria were significant predictors for overall survival (OS). Multivariable analysis showed only Qual4PS (HR: 15.41; P = 0.005) and AJCC stage (HR: 2.47; P = 0.007) were significant independent variables. The 2-year OS rates of Qual4PS(‒) patients undergoing CRT alone (68.4%) and patients undergoing trimodality therapy (62.5%) were not significant different, but the 2-year OS rates of Qual4PS(+) patients undergoing CRT alone (10.0%) were significantly lower than in patients undergoing trimodality therapy (42.1%). CONCLUSIONS: The Qual4PS criterion is reproducible for assessing the response of ESCC to CRT, and valuable for predicting survival. It may add value to response-adapted treatment for ESCC patients, and help to decide whether surgery is warranted after CRT.

Cerebral Perfusion Insufficiency and Relationships with Cognitive Deficits in Alzheimer's Disease: A Multiparametric Neuroimaging Study.

Micro- or macro-circulatory insufficiency has a negative impact in patients with Alzheimer's disease (AD). This study used arterial spin-labeled magnetic resonance imaging (ASL-MRI) and ethylcysteinate dimer single-photon emission computed tomography (ECD-SPECT) in 50 patients with AD and 30 age-matched controls to investigate how hypoperfusion patterns were associated with gray matter atrophy and clinical data. All participants completed 3DT1-MRI, ECD-SPECT and ASL-MRI examinations. Medial temporal cortex (MTC) volumes were correlated with regional signals showing significantly lower relative cerebral blood flow (rCBF) in ASL-MRI or perfusion index (PI) in ECD-SPECT. Neurobehavioral scores served as the outcome measures. Regions with lower PI showed spatial similarities with atrophy in the medial, anterior and superior temporal lobes, posterior cingulate cortex and angular gyrus, while regions showing lower rCBF were localized to the distal branches of posterior cerebral artery territories (posterior parietal and inferior temporal lobe) and watershed areas (angular gyrus, precuneus, posterior cingulate gyrus and middle frontal cortex). rCBF values in watershed areas correlated with MTC volumes and language composite scores. Precuneus and angular gyrus hypoperfusion were associated with the corresponding cortical atrophy. Macro- or micro-vasculature perfusion integrities and cortical atrophy determined the overall perfusion imaging topography and contributed differently to the clinical outcomes.

Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice.

Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer's disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.

Toxic Metals Increase Serum Tumor Necrosis Factor-α Levels, Modified by Essential Elements and Different Types of Tumor Necrosis Factor-α Promoter Single-nucleotide Polymorphisms.

BACKGROUND: Lead (Pb), cadmium (Cd), and arsenic (As) could cause health issues through oxidative stress that is indicated in the elevated tumor necrosis factor-alpha (TNF-α). However, some of the essential elements-selenium (Se), zinc (Zn), cobalt (Co), and copper (Cu)-are cofactors or structural components of antioxidant enzymes. It is suggested that single-nucleotide polymorphisms (SNPs) in the TNF-α gene have different TNF-α responses. This study aims to evaluate the effect of serum TNF-α levels through the interactions between toxic metals and essential elements and how the interactions between the toxic metals and TNF-α SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238 G > A) influence serum TNF-α levels. METHODS: Blood samples were collected from 455 workers who carried out annual health examinations and multielements determined by inductively coupled plasma mass spectrometry (ICP-MS). TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA). TNF-α promoter SNPs were analyzed by specific primer probes using real-time polymerase chain reaction (PCR) methods. RESULTS: Increasing blood Pb, Cd, and As levels were associated with elevated TNF-α levels. The interaction between Pb and Cu decreased TNF-α levels and so did the interaction between Cd and Se. In the interaction between Pb and SNPs, individuals with AA/AG (-308 G > A) and AA/AG (-238 G > A) had higher serum TNF-α levels. However, lower TNF-α levels were noted in those individuals with AA/CA (-863 C > A). In the interaction between As and SNPs, workers with AA/AG (-238 G > A) had synergic effect with As and induced higher serum TNF-α levels. CONCLUSIONS: Blood Cu and Se were antagonists of toxic metals (Pb, As, and Cd) through lower serum TNF-α levels. Variant types of TNF-α SNPs (-308 G > A, -238 G > A) and wild type of -863 CC would be more susceptible to toxic metals.

Correlation between Dopamine Transporter Degradation and Striatocortical Network Alteration in Parkinson's Disease.

The association between dopamine neuron loss and functional change in the striatocortical network was analyzed in 31 patients with Parkinson's disease (PD) [mean disease duration 4.03 ± 4.20 years; Hoehn and Yahr (HY) stage 2.2 ± 1.2] and 37 age-matched normal control subjects. We performed 99mTc-TRODAT-1 SPECT/CT imaging to detect neuron losses and resting-state functional magnetic resonance imaging to detect functional changes. Mean striatal dopamine transporter binding ratios were determined by region of interest analysis. The functional connectivity correlation coefficient (fc-cc) was determined in six striatal subregions, and interactions between these binding ratios and the striatocortical fc-cc values were analyzed. The PD patients had significant functional network alterations in all striatal subregions. Lower striatal dopamine transporter binding correlated significantly with lower fc-cc values in the superior medial frontal (SMF) lobe and superior frontal lobe and higher fc-cc values in the cerebellum and parahippocampus. The difference in fc-cc between the ventral inferior striatum and SMF lobe was significantly correlated with increased disease duration (r = -0.533, P = 0.004), higher HY stage (r = -0.431, P = 0.020), and lower activities of daily living score (r = 0.369, P = 0.049). The correlation of frontostriatal network changes with clinical manifestations suggests that fc-cc may serve as a surrogate marker of disease progression.

Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation, amyloid deposition and cognition impairment in metabolically stressed APPswe/PS1dE9 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome and vascular dysfunction was suggested to be the risk factors for Alzheimer's disease (AD). Xuefu Zhuyu decoction (XZD) is a traditional Chinese medicine used to treat metabolic syndrome and cardiac-cerebral vascular disease. The effects of XZD on ameliorating metabolic syndrome, amyloid-related pathologies and cognitive impairment in an animal model of AD with metabolic stress was investigated. MATERIALS AND METHOD: The animal model of AD with metabolic stress was created by administrating high-fat diet and a low-dose injection of streptozotocin prior to the appearance of senile plaques in APP/PS1 transgenic mice. The diabesity-associated metabolic changes and AD-related pathological alterations were examined. RESULTS: We found that XZD reduced body weight, insulin and leptin level, HOMA-IR, hepatic triglyceride, serum Aß42 in the metabolic stressed AD animal. XZD also ameliorated oral glucose tolerant, Aß deposition, astrocyte and microglia activation in the vicinity of plaques, and nesting behavior in the metabolic stressed AD animal. CONCLUSION: The results of this study suggest that XZD is able to reduce the peripheral metabolic stress-mediated vascular hypoperfusion, neuroinflammation and AD-related pathology in APP/PS1 mice.

The association of the blood lead level and serum lipid concentrations may be modified by the genetic combination of the metallothionein 2A polymorphisms rs10636 GC and rs28366003 AA.

BACKGROUND: Lead in blood can stimulate lipid oxidation in phosphatidylcholine and increase peroxidation in lipids. Metallothionein (MT) is a cysteine-rich protein that can influence the detoxification of heavy metals and scavenge oxidative stress for free radicals. One of the most expressive functional genes in humans is the MT2A gene. OBJECTIVE: This study aims to determine if the association of the blood lead level and lipid biomarkers was influenced by MT2A polymorphisms. METHODS: We recruited 677 participants after informed consent was obtained. All the samples collected were analyzed for lipid biomarkers and blood lead levels and were genotyped for MT2A polymorphisms by reverse transcription polymerase chain reaction. A short questionnaire collected the medical history and alcohol and cigarette consumption information. The data were used for descriptive analyses and linear regression models. RESULTS: The investigation revealed that lead elevated concentration increased low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol (HDL-C) by multiple linear models. The carriers of the rs10636 GC-rs28366003 AA genetic combination may be less susceptive to lead elevated concentration on HDL-C than other types. CONCLUSION: In conclusion, the association of the blood lead level and HDL-C may be modified by the MT2A genetic combination: the rs10636 GC-rs28366003 AA genotype could play a protective role in lead elevated concentration on HDL-C in humans.

Parkinson's disease: diagnostic utility of volumetric imaging.

PURPOSE: This paper aims to examine the effectiveness of structural imaging as an aid in the diagnosis of Parkinson's disease (PD). METHODS: High-resolution T 1-weighted magnetic resonance imaging was performed in 72 patients with idiopathic PD (mean age, 61.08 years) and 73 healthy subjects (mean age, 58.96 years). The whole brain was parcellated into 95 regions of interest using composite anatomical atlases, and region volumes were calculated. Three diagnostic classifiers were constructed using binary multiple logistic regression modeling: the (i) basal ganglion prior classifier, (ii) data-driven classifier, and (iii) basal ganglion prior/data-driven hybrid classifier. Leave-one-out cross validation was used to unbiasedly evaluate the predictive accuracy of imaging features. Pearson's correlation analysis was further performed to correlate outcome measurement using the best PD classifier with disease severity. RESULTS: Smaller volume in susceptible regions is diagnostic for Parkinson's disease. Compared with the other two classifiers, the basal ganglion prior/data-driven hybrid classifier had the highest diagnostic reliability with a sensitivity of 74%, specificity of 75%, and accuracy of 74%. Furthermore, outcome measurement using this classifier was associated with disease severity. CONCLUSIONS: Brain structural volumetric analysis with multiple logistic regression modeling can be a complementary tool for diagnosing PD.

FDG PET using SUVmax for preoperative T-staging of esophageal squamous cell carcinoma with and without neoadjuvant chemoradiotherapy.

BACKGROUND: Accurate T-staging is pivotal for predicting prognosis and selecting appropriate therapies for esophageal squamous cell carcinoma (ESCC). The diagnostic performance of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for its T-staging is uncertain. We investigated use of FDG PET/CT for preoperative T-staging of patients with ESCC. METHODS: Patients with ESCC given preoperative FDG PET/CT scans, either with (CRT[+] group) or without (CRT[-] group) neoadjuvant chemoradiotherapy, were retrospectively reviewed. Maximal standardized uptake value (SUVmax) of the primary tumors on FDG PET/CT scans were measured, and histopathological results were used as the reference standard. The associations between pathological T-stage and potential factors of age, tumor location, tumor grade, tumor size, and tumor SUVmax were analyzed. The cut-off levels of SUVmax for predicting different T-stages and for residual viable tumors after neoadjuvant chemoradiotherapy were determined using receiver operating characteristic analyses. RESULTS: We enrolled 103 patients (45 in the CRT[-] group; 58 in the CRT[+] group). SUVmax, an independent predictive factor, positively correlated with the pathological T-stage in both groups (CRT[-] group: ρ = 0.736, p < 0.001; and CRT[+] group: ρ = 0.792, p < 0.001). The overall accuracy of the PET/CT with thresholded SUVmax for predicting the pathological T-stage was 73.3% in the CRT[-] group (SUVmax of T0: 0-1.9, T1: 2.0-4.4, T2: 4.5-6.5, T3: 6.6-13.0, T4: >13.0) and 67.2% in the CRT[+] group (SUVmax of T0: 0-3.4, T1: 3.5-3.9, T2: 4.0-5.5, T3: 5.6-6.2, T4: > 6.2). For CRT[-] group, the accuracy using an SUVmax cut-off of 4.4 to differentiate early (T0-1) from locally advanced disease (T2-4) was 82.2% (95% CI, 71.1-93.4%). For CRT[+] group, the accuracy using an SUVmax cut-off of 3.4 to predict residual viable tumors (non-T0) after completion of chemoradiotherapy was 82.8% (95% CI, 73.0-92.5%). CONCLUSIONS: The FDG avidity of a primary esophageal tumor significantly positively correlated with the pathological T-stage. PET/CT with thresholded SUVmax was useful for predicting T-stage and differentiating residual viable tumors.

Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson's Disease.

Parkinson's disease (PD) is the most second common neurodegenerative movement disorder. Neuroinflammation due to systemic inflammation and elevated oxidative stress is considered a major factor promoting the pathogenesis of PD, but the relationship of structural brain imaging parameters to clinical inflammatory markers has not been well studied. Our aim was to evaluate the association of magnetic resonance spectroscopy (MRS) measures with inflammatory markers. Blood samples were collected from 33 patients with newly diagnosed PD and 30 healthy volunteers. MRS data including levels of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) were measured in the bilateral basal ganglia and cerebellum. Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes were significantly different between PD patients and normal healthy volunteers. Significant positive correlations were noted between MRS measures and inflammatory marker levels. In conclusion, patients with PD seem to have abnormal levels of inflammatory markers in the peripheral circulation and deficits in MRS measures in the dominant basal ganglion and cerebellum.

Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO.

BACKGROUND: The accumulation of soluble oligomeric amyloid-ß peptide (oAß) proceeding the formation of senile plaques contributes to synaptic and memory deficits in Alzheimer's disease. Our previous studies have indentified scavenger receptor A (SR-A), especially SR-A type I (SR-AI), as prominent scavenger receptors on mediating oAß clearance by microglia while glycan moiety and scavenger receptor cysteine-rich (SRCR) domain may play the critical role. Macrophage receptor with collagenous structure (MARCO), another member of class A superfamily with a highly conserved SRCR domain, may also play the similar role on oAß internalization. However, the role of N-glycosylation and SRCR domain of SR-AI and MARCO on oAß internalization remains unclear. RESULT: We found that oAß internalization was diminished in the cells expressing SR-AI harboring mutations of dual N-glycosylation sites (i.e. N120Q-N143Q and N143Q-N184Q) while they were normally surface targeted. Normal oAß internalization was observed in 10 SR-AI-SRCR and 4 MARCO-SRCR surface targeted mutants. Alternatively, the SRCR mutants at ß-sheet and α-helix and on disulfide bone formation obstructed receptor's N-glycosylation and surface targeting. CONCLUSION: Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAß internalization.

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

Brain mediators of systemic oxidative stress on perceptual impairments in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is well documented to be associated with elevated systemic oxidative stress and perceptual impairments. Furthermore, the striatum and extrastriatal cortical areas, which are involved in the coordination of perceptual functions, are impaired at an early stage of the disease. However, the possible pathophysiology involved in perceptual impairments remains unclear. This raises the possibility that structural abnormalities might mediate the relationship between oxidative stress and perceptual impairments. METHODS: We explored the differences between 27 patients with PD and 25 healthy controls in terms of serum oxidative stress, perceptual functions, and regional gray matter. A single-level three-variable mediation model was used to investigate the possible relationships between serum oxidative stress, regional gray matter volume, and different domains of perceptual functioning. RESULTS: The results demonstrate that increased serum oxidative stress (as indicated by thiobarbituric acid reactive substances) was associated with declined perceptual functioning in PD patients. We further explored significant gray matter volume reductions in the bilateral temporal gyri (middle temporal gyrus and fusiform gyrus), bilateral frontal gyri, limbic lobe (hippocampus and uncus), left inferior parietal lobule, right caudate nucleus, and insula in PD. Further mediation analysis showed that gray matter volumes in the middle temporal gyrus, inferior parietal lobule, hippocampus, and insula served as brain mediators between elevated serum oxidative stress and perceptual impairments. CONCLUSIONS: These results suggest that higher oxidative stress levels adversely impact perceptual functions by causing temporal and mesolimbic abnormalities.